CN1849068A - Capsaicin derivates and the production and use thereof - Google Patents
Capsaicin derivates and the production and use thereof Download PDFInfo
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- CN1849068A CN1849068A CNA2004800260925A CN200480026092A CN1849068A CN 1849068 A CN1849068 A CN 1849068A CN A2004800260925 A CNA2004800260925 A CN A2004800260925A CN 200480026092 A CN200480026092 A CN 200480026092A CN 1849068 A CN1849068 A CN 1849068A
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/16—Antifouling paints; Underwater paints
- C09D5/1606—Antifouling paints; Underwater paints characterised by the anti-fouling agent
- C09D5/1612—Non-macromolecular compounds
- C09D5/1625—Non-macromolecular compounds organic
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/22—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/14—Paints containing biocides, e.g. fungicides, insecticides or pesticides
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/16—Antifouling paints; Underwater paints
Abstract
The invention relates to new compounds, namely capsaicin derivates, a new method for their production, and their use as micro-organism-repellent agents in paints and coatings, in particular for marine installations and ships, but also for land-based structures.
Description
The present invention relates to new compound, i.e. capsaicin derivates, the new method of its production and as the microbial protection agent at lacquer and coating, in particular for marine installation and ship, and the lacquer of land-based installation and material and the application in the coating.
Clean and level and smooth and when not having halobiontic growth when hull, advance will faster simultaneously the burn less fuel of ship in water so.
Tributyl tin (TBT) is used to stop algae and sea-plant now, shellfish, the growth on ship of ocean tulip and analog.This growth produces frictional force, thus inevitable skyrocketing with fuel cost.Therefore TBT is added to boats and ships with in coating with lacquer so that produce the lacquer of so-called " anti-sea-crust ".TBT poisons the marine organisms that are in contact with it so keeps the side of ship not have halobiontic growth.
TBT has the side effect on a large amount of environment lamentedly.TBT not only influences the marine organisms of attempting to depend on ship's side, and other marine organisms are poisoned.In addition, shown that TBT is accumulated in the marine food chain and causes the abnormal growth of multiple biology.In addition, shown that TBT causes the deformity of oyster shell body structure, the sex reversal of snail and the immunologic derangement of other marine species and neurotoxicity and hereditary change.
These find to have caused the decision ban TBT of UN International Maritime Organization (IMO) all application in marine paint.In case delivery at least 25% world tonnage or all flag countrys that constitute 25% IMO member state have ratified this treaty, this ban will come into force.No matter whether above-mentioned minimum requirements is satisfied, this treaty will come into force on January 1st, 2008 at the latest.
Therefore, will have absolute prohibition after in January, 2008 to the application of TBT in this lacquer.In addition, the protective layer lacquer that one deck prevents that TBT from contacting with water must physically be removed or apply to this lacquer in the above.
Therefore, the Avirulent microbes protective agent that can replace the TBT in the marine paint that needs other.
According to the present invention, the compound that a class is new can replace TBT as the microbial protection agent.The compound that this class is new is the new derivative of natural occuring article matter capsaicine, and described capsaicine extracts from red pepper (Capsicum annum) and other pepper fruits (Capsicum fructus).
Capsaicine ((E)-8-methyl-N-vanillyl-6-nonene acid amides) extracts as mentioned above from red pepper.Well-known this extract is as the microbial protection agent in the marine paint.Also there have been to be described in Dray N.S.Biochemical Pharmacology, 44, (1992), other the useful pharmacological characteristics in 611.
Yet the capsaicine extract has following shortcoming, makes it be not suitable as composition in " anti-sea-crust lacquer ".
At first, because this extract based on natural raw material, also have fluctuation because the natural waves movable property of raw material supply is given birth to the possibility of q.s, and supply of raw material also will be depended on the size of crop, quality, price etc.The big supply of this now raw material is very insecure.
Secondly, standardization capsaicine extract comprises at least 3 kinds of isomer, has different chemical property and be difficult to distinguish.Therefore may be difficult to obtain to have and be used for the abundant homogeneous purity that purpose uses and the capsaicine extract of composition.
The 3rd, modern marine paint be based on protective agent and polymeric substrates chemical bonding in case protective agent be flushed in the seawater immediately.Thisly be bonded to the protective agent of polymer base and the reaction of seawater and polymeric substrates discharges synchronously.The hydrophily of protective agent is low more, and the service life of marine paint will be long more.Natural capsaicine extract is made up of the isomer of several different chemical character and the water-soluble pH value along with water of these isomer changes and changes.Based on natural capsaicine extract, this will cause that protective agent product dissolubility does not need and uncontrollable variation.
From United States Patent (USP) 5,143,545 recognize a kind of anti-sea-crust lacquer that contains the antibiotics activating agent of similar for example chloramphenicol.The danger of the antibiotic resistance that constitutes by this antibiotic propagation that is used for resisting the human infectious disease shows the application that avoid this active component of anti-sea-crust lacquer.
From United States Patent (USP) 5,226,380 recognize a kind of anti-sea-crust lacquer that contains hot red pepper or capsicum oleoresin derivative as the particle of activating agent.These activating agents based on capsaicine or hot red pepper are subjected to identical restriction in aforesaid raw material supply.This also is applicable to United States Patent (USP) 5,397,385 anti-sea-crust lacquer.It comprises the capsaicine as the fine-powdered of active component, the liquid solution of capsicum oleoresin or crystallization capsaicine.United States Patent (USP) 5,629,045 also describe a kind of contain capsaicine and have alkyl derive the vanillyl amide derivative of base as the anti-sea-crust lacquer of active component.The generation of vanillyl amide derivative is based on the extract of capsaicine.United States Patent (USP) 5,698,191 lacquer also comprise the capsicum oleoresin of combination Saponaria officinalis glycoside compound.
An object of the present invention is to provide the substitute of the TBT that does not have toxicity and in marine food chain, do not accumulate.
Another object of the present invention provides the substitute of the capsaicine product of previously known, thereby avoids the problem of raw-material unreliable supply and price and quality fluctuation.
Another object of the present invention provides the substitute of known capsaicine product, and it can determine that composition and high product purity produce.
Another object of the present invention provides the substitute of known capsaicine product, and it has the hydrophily of determining and/or reducing.
The another one purpose provides has the product that broad-spectrum biological is learned activity.
Another purpose provides has the ecological protective agent product that distributes of acceptable.
These purposes are achieved by the feature that is described below the claim qualification of enclosing.
According to the invention provides new compound, can be called the new capsaicine alkynes analog of phenyl capsaicine.New compound of the present invention is characterised in that the compound of following formula (1),
Wherein R is selected from alkyl, thiazolinyl, alkynyl, pi-allyl, aryl, alkoxyl, aryloxy group, alkanoyl, aroyl, amino, alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl, cycloalkenyl group, halogen, hydroxyl, oxygen, nitro, the substituting group of trifluoromethyl; When described substituent R comprises carbochain, can be straight chain or side chain, also can use alkyl, thiazolinyl; alkynyl, pi-allyl, aryl, alkoxyl; aryloxy group, alkanoyl, aroyl, amino; the alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl; cycloalkenyl group, halogen, hydroxyl; oxygen, nitro, trifluoromethyl further replaces.
When R comprised carbochain, carbochain had from 1 to 8 carbon atom, more preferably from 2 to 6 carbon atom.Another organizes preferred formula (1) compound is to have carbochain among those R to be the long compound of 1-4 carbon atom.
In the especially preferred compound group, R is the alkyl with 1-4 carbon atom, and the R in the most preferred is isopropyl or propyl group.
Formula (1) compound can be the carboxylic acid derivates (3) of HO or carboxylic acid transforms production (1) with vanillyl ammonia capsaicin derivates generation by Z usually shown in following response diagram A:
Z＝Cl，OH，R
1O,NR
1 2
R
1=alkyl
R is selected from alkyl, thiazolinyl, alkynyl, pi-allyl, aryl, alkoxyl, aryloxy group, alkanoyl, aroyl, amino, alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl, cycloalkenyl group, halogen, hydroxyl, oxygen, nitro, the substituting group of trifluoromethyl; When described substituent R contains carbochain, can be straight chain or side chain, also can use alkyl, thiazolinyl; alkynyl, pi-allyl, aryl, alkoxyl; aryloxy group, alkanoyl, aroyl, amino; the alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl; cycloalkenyl group, halogen, hydroxyl; oxygen, nitro, trifluoromethyl further replaces.
Carboxylic acid derivates (3) is meant and comprises arbitrary reactant that is used for the reaction shown in the response diagram A, and may most preferably be ester, acid amides or acid chloride.In this manual, term " carboxylic acid derivates (3) " also comprises carboxylic acid (4) itself.
Vanillyl ammoniate (2) from vanillic aldehyde can be by Kaga, H., Miura, M. and Kazuhiko, O., J.Org.Chem.54 (1989) 3477 described generations.Obtain 42% productive rate.
Other reactant, compound (3) or (4) can produce through the following steps:
5-chloro-1-amylalcohol (7) with protection transforms the acetylene alcohol compound (6) that acetylenic compound (8) produces protection;
Produce free acetylene alcohol compound (5) from compound (6) decomposing protection base;
Oxidized compound (5) produces carboxylic acid (4); And
Perhaps acid (4) is transformed into carboxyl acyl chloride (3).
Reaction sequence is shown in down among the response diagram B:
R is selected from alkyl, thiazolinyl, alkynyl, pi-allyl, aryl, alkoxyl, aryloxy group, alkanoyl, aroyl, amino, alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl, cycloalkenyl group, halogen, hydroxyl, oxygen, nitro, the substituting group of trifluoromethyl; When described substituent R comprises carbochain, can be straight chain or side chain, also can use alkyl, thiazolinyl; alkynyl, pi-allyl, aryl, alkoxyl; aryloxy group, alkanoyl, aroyl, amino; the alkyl sulfenyl, artyl sulfo, cyano group, cycloalkyl; cycloalkenyl group, halogen, hydroxyl; oxygen, nitro, trifluoromethyl further replaces.
The new capsaicine alkynes analog that has formula (1) in one embodiment of the invention can be used as the microbial protection agent.The microbial protection agent can be separately or is included in to produce in lacquer or the coating as the composition of microbial protection agent composition prevents the finished product that microorganism and other living organisms grow on the surface of having used this product.
Described reagent or mixture can add in lacquer or the coating, make the concentration that exists of active formula (1) compound be 0.1-50%, the concentration of 0.2-10% especially by weight by weight.The most preferable concentrations that formula (1) compound is added in lacquer or the coating is 0.5-5%, the concentration of 0.3-1% especially by weight by weight.
One embodiment of the invention are the microbial protection agent that comprise two or more formulas (1) combination of compounds.
Another embodiment of the present invention is the microbial protection agent that comprises the combination of formula (1) compound and another microbial protection agent.
Another embodiment of the present invention is the microbial protection agent composition, its Chinese style (1) compound and one or multiple inert additwe, and such as solvent, viscosity modifier, i.e. thinner or thickener; And/or preservative is included in the mixture.
Another embodiment of the present invention is lacquer or coating, has wherein added microbial protection agent of the present invention or mixture in order to avoid microorganism or other atom, as SeaShell, and algae, ocean tulip, sea-plant and fungi growth.This lacquer is called " anti-sea-crust " lacquer and is mainly used in ship, particularly hull, perhaps marine installation, and such as the shell of solution environmental, wharf structure and harbour.Also can use microbial protection agent of the present invention or mixture in coating, described coating can be applied on the coat of paint for example so that form the watertight surface or have the surface of other desired characteristic.
Another embodiment of the present invention is corresponding to being used for onshore applications and structure as mentioned above, especially based on wood such as timber, the lacquer of wooden plate etc. or coating.
Biologic test
In order to illustrate the biologic activity of capsaicine, carried out biologic test as described below.This experiment shows that capsaicine has biologic activity of the present invention and effect.In other hull bottom material or lacquer, capsaicine and/or other formula (1) compound can obtain other activity under the used concentration of this experiment.
Experiment flow
Capsaicine sneaked into state in the commercially available shipbottom paint that does not contain bactericide.The trade mark of lacquer Fabio Eco by name
TMAnd by International Paint, Akzo-Nobel produces.Every kg lacquer 0g, 1g produces 3 kinds of different concentration with the 5g capsaicine.The thinner (International No.3) that at first capsaicine is dissolved in 10ml is sneaked into lacquer then.Only the mixture of the thinner of Fabio Eco and 10ml is used as contrast.To coat with lacquer mixture before using left standstill 1 hour.Lacquer is applied to a large amount of poly (methyl methacrylate) plates (on 11 * 11 * 0.2cm).
Give 15 plate japannings altogether.
Contrast lacquer (0g/kg capsaicine) on 5 blocks of plates
The capsaicine of 1g/kg on 5 allegros
The capsaicine of 5g/kg on 5 allegros
To coat with lacquer plate 21 ℃ of standing and drying 24 hours according to the regulation of manufacturer.To coat with lacquer plate and be installed on the aluminium chassis, and on the test raft, reach the following 0.5-1m in sea.It is outdoor that the test raft is placed on the boats and ships Bioexperiment of depth of water 10m.The lacquer plate is placed the time period from July 4 calendar year 2001 to August 31 calendar year 2001.This time period is that marine organisms at first are the most intensive periods of ocean tulip (Balanusimprovisus) growth on the hull.Fetching the lacquer plate then analyzes immediately.
The analysis of growth
Carry out following lacquer plate analysis:
The lacquer plate is taken pictures.
Estimate the cover degree of ocean tulip (Balanus improvisus).Estimate the cover degree of Mytilus galloprovincialis (Mytilus edulis).Scrape all growth-gens on the coating removal plate and determine weight in wet base.
Accompanying drawing
Illustrated experimental result shows that the processing comparison by coat with lacquer 5g capsaicine concentration with every kg obtains remarkable low growth according to handling among Fig. 1-6.
Fig. 1 shows the cover degree with the ocean tulip (Balanusimprovisus) of 3 kinds of different surface treatment in bar chart.Bar chart is represented the mean value and the standard deviation of 5 repetitions.
Thus chart as can be seen other 2 kinds of surface ratio of per kilogram lacquer 5g Capsaicin Treatment handle cover degree significantly low (the 1-factorial analysis of difference, F
2,12=40.5; P＜0.0001).Growth is reduced to by 74% of ocean tulip cover degree mensuration.
Fig. 2 shows the cover degree of the Mytilus galloprovincialis (Mytilus edulis) that same procedure is as described in Figure 1 measured.Bar chart is represented the mean value and the standard deviation of 5 repetitions.
Bar chart does not have statistically evident difference (the 1-factorial analysis of difference, F as can be seen between 3 processing thus
2,12=3.0; P＞0.05).
Fig. 3 shows the weight in wet base of total growth-gen on the lacquer plate of 3 different disposal.Bar chart is represented the mean value and the standard deviation of 5 repetitions.
Show as can be seen thus, the capsaicine of per kilogram lacquer 5g is compared growth-gen significantly low (the 1-factorial analysis of difference, F with two other processing
2,12=12.6; P＜0.001).Growth is reduced to by total growth-gen weight in wet base and reduces 64% of mensuration.
Fig. 4 shows the figure (0g/kg) on 5 surfaces of handling with the contrast lacquer.
Fig. 5 shows the figure on 5 surfaces of handling with the least concentration of 1g/kg.
Fig. 6 shows the figure on 5 surfaces of handling with the maximum concentration of 5g/kg.The growth-gen that relatively can know the surface ratio contrast surface of finding out among Fig. 6 by naked eyes is significantly low.
The synthesis strategy of synthesis of phenyl capsaicine and test
The following synthetic in detail description that has provided noval chemical compound.Some documents of collecting in the list of documents of listing with reference to some endings place.The synthetic method of known several capsaicine and other capsaicine class things.
5-9Under situation of the present invention, capsaicine is a particular importance to the biologic activity of boats and ships microorganism.In order to produce more effective capsaicine class thing, developed the synthesis strategy of capsaicin derivates, wherein carbon-carbon double bond is substituted by carbon carbon triple bond.General synthesis strategy is presented in the chart 1.
The reverse synthesis analysis of chart 1. capsaicine alkynes analogs.
The synthesis strategy of capsaicine alkynes analog generally is at alkynyl material 8 (R=aryl, alkyl or the like).By changing the R-group, can synthesize different capsaicine alkynes analogs, and can estimate according to biologic activity thus.First target molecule 1 (R=Ph) produce the alkynes benzyne (8: R=Ph) and 4-hydroxy 3-methoxybenzene formaldehyde (vanillin) (4) and 5-chloro-1-amylalcohol (11) as base material.4-amino methyl-2-metoxyphenol (vanillyl ammonia) (2) is synthetic by vanillic aldehyde (4) described in document.
65-chloro-1-amylalcohol (11) at first protects as THP ether by utilizing the standard reaction condition.
10,11The productive rate of corresponding THP ether (10) is 95%.Substitution reaction (S with the THF solution of phenyl ethynylation lithium
N2) do not produce the product (7) of expectation, because observe phenyl ethynylation lithium and the HCl (E that eliminates as the base material reaction from 10
2) the result be that corresponding alkene is the product of unique formation.Phenyl ethynylation sodium produces identical result.This problem changes into corresponding iodine analog 9 by 10 and is solved in Finkelstein reaction (Frinkelstein reaction).
11-13Present substitution reaction is carried out finely and is formed the alkynes 7 of 85% productive rate.Acid catalysis is removed the THP protection in 7
10Produce the alcohol 6 of almost quantitative productive rate (97%).Brown ' s chromic acid the oxidation of modification
14Produce the carboxylic acid 5 of 90% productive rate.React with thionyl chloride 5 then, form the corresponding acid chloride 3 of 85% productive rate.With the coupling reaction of acid chloride (3) and vanillyl ammonia (2) produce 86% productive rate target molecule 7-phenyl oneself-6-alkynes-acid-4-hydroxy 3-methoxybenzene methyl acid amides (1), known to the inventor, do not have the people synthetic at present as yet.The inventor advises that the phenyl capsaicine is as 1 popular name.
Chart 2. experiments
Summary:
On Varian 300MHz spectrometer, obtain nuclear magnetic resoance spectrum, NRM 300MHz
1H-NMR spectrum and 75MHz
13The C-NMR spectrum.Tetramethylsilane (TMS) is used as internal standard.
1The chemical shift of H-NMR spectrum is shown as the ppm with respect to TMS.
13The C-NMR spectrum is shown as the ppm (δ 76.9ppm) with respect to the deuterate chloroform.On Fluka silica gel plate (silica gel/DC-Alufolien silica gel with fluorescence indicator, production number 60778), carry out thin-layer chromatography.With ultraviolet (UV) (λ=254nm) or with MOP reagent ((molybdato-phosphoric acid (5g), cerous sulfate (IV) are (2g) and 98 W H for ethanol (125mL) solution of molyb-dato-phosphoric acid (14g) or CER-MOP reagent
2SO
4Water (16ml) (mL)) solution, and by launching to detect point sample with hot-air syringe heating silica gel plate.Chemical reagent is by Fluka, Sigma Aldrich, and Acros, Merck and Lancaster provides.Use the standard seasoning when needing.Dry tetrahydrofuran is produced by benzophenone sodium ketyl under the argon gas.
With 2-(5-chlorine amyl group oxygen) tetrahydrochysene-2H-pyrans (10):
(12.26g 0.1mol) is dissolved in the dry methylene chloride (400mL) 5-chloro-1-amylalcohol.Add 3 then, 4-dihydro-2H-pyrans (12.62g, 0.15mol) and pyridine toluene-4-sulfonic acid salt (1.26g, the magnetic agitation reactant mixture 5mmol) and at room temperature spends the night in the nitrogen.Add saturated solution of sodium bicarbonate (150mL) and separate this phase.(4 * 5mL) extract this water to use carrene then.(2 * 20mL) clean the dry then mutually (MgSO of the carrene that merges to water
4).Distilled dichloromethane and produce 19 on rotary evaporator then.The light yellow oil of 6g (95%).Nuclear magnetic resonnance shows pure product.
2-(5-iodine amyl group oxygen) tetrahydro-2H-pyrans (9):
(20.67g, dry acetone 0.1mol) (50mL) solution dropwise add the sodium iodide of magnetic agitation to, and (16.49g is in dry acetone 0.11mol) (150mL) solution with 2-(5-chlorine amyl group oxygen) tetrahydro-2H-pyrans (10).Refluxed overnight reactant mixture in nitrogen.After the cooling, leach the sodium chloride of precipitation and on rotary evaporator, distill out acetone.Still the residue that contains some sodium chloride is dissolved in the dry pentane (200mL).Leach sodium chloride and on rotary evaporator, distill out pentane, produce the yellowish-brown oil of 26.2g (88%).NMR shows pure product.
2-(7-phenyl oneself-6-alkynyloxy) tetrahydro-2H-pyrans (7):
With BuLi (33.3mL, 50mmol, 1.5M) under nitrogen 0 ℃ of phenylacetylene that dropwise adds magnetic agitation to (5.11g is in dry tetrahydrofuran 50mmol) (200mL) solution.After having added all BuLi, 0 ℃ of stirred reaction mixture 30 minutes.Dropwise add 2-(5-iodine amyl group oxygen) tetrahydro-2H-pyrans (9) (14.91g, dry tetrahydrofuran 50mmol) (100mL) solution at 0 ℃.After interpolation is finished, make reactant mixture reach room temperature refluxed overnight then in turn.By thin-layer chromatography (TLC) monitoring reaction.When all base materials transform, add water (300mL) and use benzinum (boiling point 40-60 ℃) (6 * 50mL) extraction waters.(4 * 25mL) clean the dry then (MgSO of the organic facies that merges to water
4).On rotary evaporator, distill out benzinum, produce 11.6g (85%).NMR shows pure product, does not therefore need further purifying.
The 7-phenyl oneself-6-alkynes-1-alcohol (6):
With pyridine toluene-4-sulfonic acid salt (0.75g, 3mmol) add to give magnetic agitation 2-(7-phenyl oneself-6-alkynyloxy)-(13.62g is in dry methyl alcohol (300mL) solution 50mmol) for tetrahydrochysene-2H-pyrans (7).Monitor at 55 ℃ of stirred reaction mixtures and by TLC.After all base materials transform, on rotary evaporator, distill out methyl alcohol and add water (200mL) to residue.With benzinum (boiling point 40-60 ℃)/Et
2O1: 1 (5 * 50mL) extraction waters.(2 * 20mL) clean the dry then (MgSO of the organic facies that merges to water
4).Distillation produces the yellow viscous oil of 9.1g (97%) on rotary evaporator.TLC and NMR show pure products.
The 7-phenyl oneself-6-acetylenic acid (5):
At 0 ℃, with Brown ' s chromic acid reagent (133mL, 88mmol, 0,66M) dropwise add to give lentamente magnetic agitation the 7-phenyl oneself-6-alkynes-1-alcohol (6) (7.53g, acetone 40mmol) (400mL) solution.After having added chromic acid, 0 ℃ then at room temperature stirred reaction mixture 1 hour show that up to TLC all base materials all transform.Add water (300mL) and use benzinum (boiling point 40-60 ℃)/Et
2O1: 1 (6 * 50mL) extraction waters.(2 * 25mL) clean the dry then (MgSO of the organic facies that merges to water
4).Distillation produces the light yellow viscous oil of 7.3g (90%), crystallization when leaving standstill on rotary evaporator.TLC and NMR show pure products.
The 7-phenyl oneself-6-alkynes acid chloride (3):
With the 7-phenyl oneself-6-acetylenic acid (5) (4.05g, 20mmol) and thionyl chloride (7.14g, 60mmol) mixture of magnetic agitation backflow (100 ℃) is 2 hours.On rotary evaporator, remove unnecessary thionyl chloride, produce the brown oil of 3.7g (85%).TLC and NMR show pure products.
Vanillyl ammonia (2):
Vanillyl ammonia as synthetic 100mmol tolerance as described in the document.
6
The 7-phenyl oneself-6-alkynes-acid-4-hydroxy 3-methoxybenzene methyl acid amides (phenyl capsaicine) (1):
In the argon gas dropwise with the 7-phenyl oneself-6-alkynes acyl chlorides (3) (10mmol, dry Et 2.21g)
2O (25mL) solution adds vanillyl ammonia (2) (3.06g, dry Et 20mmol) to
2In the suspension of O (75mL).Reaction mixture refluxed shows that up to TLC base material transforms.On rotary evaporator, remove diethyl ether, produce the yellow viscous oil of 2.9g (86%), crystallization when leaving standstill.TLC and NMR show pure products.
List of references
[1]A.Dray，Biochem.Pharmacol.1992，44，611.
[2]M.J.Caterina，M.A.Schumacher，M.Tominaga，T.A.
Rosen，J.D.Levine.D.Julius，Nature?1997，389，816.
[3]P.Holzer，Pharmacol.Rev.1991，43，143.
[4]T.R.LaHahn，R.W.Farmer，Proc.West.Pharmacol?Soc.1983，26，145
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Claims (11)
1. a compound is characterized in that having general formula (1),
Wherein R is for being selected from alkyl, thiazolinyl, alkynyl, pi-allyl, aryl; alkoxyl, aryloxy group, alkanoyl, aroyl; amino, alkyl sulfenyl, artyl sulfo, cyano group; cycloalkyl, cycloalkenyl group, halogen, hydroxyl; oxygen when nitro, the substituting group of trifluoromethyl comprise carbochain when described substituent R, can be straight chain or side chain; also can be by alkyl, thiazolinyl, alkynyl, pi-allyl; aryl, alkoxyl, aryloxy group, alkanoyl; aroyl, amino, alkyl sulfenyl, artyl sulfo; cyano group, cycloalkyl, cycloalkenyl group, halogen; hydroxyl, oxygen, nitro, trifluoromethyl further replaces.
2. according to the compound of claim 1, wherein R is the alkyl with 1-4 carbon atom.
3. according to the compound of claim 1, wherein R is propyl group or isopropyl.
4. produce the method for compound, it is characterized in that transforming the capsaicin derivates of carboxylic acid (4) or carboxylic acid derivates (3) production (1) with vanillyl ammonia (2) with formula (1).
5. according to the method for claim 4, it is characterized in that further following steps:
5-chloro-1-amylalcohol (7) with protection transforms the acetylene alcohol compound (6) that acetylenic compound (8) produces protection;
From compound (6) decomposing protection base so that produce free acetylene alcohol compound (5);
Oxidized compound (5) is so that produce acetylene series carboxylic acid (4);
Perhaps carboxylic acid (4) is changed into carboxylic acid derivates (3), especially acid chloride (3).
6. according to formula (1) compound of claim 1, be used as microbial protection agent material.
7. the application of the formula of claim 1 (1) compound in production microbial protection agent composition.
8. the formula of claim 1 (1) compound is used for the application of the lacquer or the coating of ship in production.
9. the formula of claim 1 (1) compound is used for the application of the lacquer or the coating of marine installation in production.
10. the formula of claim 1 (1) compound is used for the wooden lacquer or the application of coating in production.
11. the formula of claim 1 (1) compound is used for the application of the lacquer or the coating of onshore applications in production.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20034069A NO20034069L (en) | 2003-09-12 | 2003-09-12 | Preparation and use of capsaicin derivatives |
| NO20034069 | 2003-09-12 |
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| CN100415095C CN100415095C (en) | 2008-09-03 |
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| JPH09100202A (en) * | 1995-10-03 | 1997-04-15 | Meiji Milk Prod Co Ltd | Anti-organism agent |
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| CN104927585B (en) * | 2015-07-13 | 2018-10-16 | 上海金泛斯标识有限公司 | Luminous paint for jet-printed advertisements |
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